1. Applications of Photosensitisers to Cancer, Viral, Bacterial Disease and Immunology
Terry Wright

2. Non-toxic Sensitizer Cell Survives Photosensitising agent Dye molecule
Not cytotoxic
Taken up by cell
(i.e. staining)
Cell
Cell Survives

3. Tuned Laser Light Cell Survives Light exposure Red or near IR
Light (Red)
Light exposure
Red or near IR
Cell is transparent
Not cytotoxic
No heating
Cell
Cell Survives

4. Cell Dies!! ROS Flood = Death PS + Light Cell not transparent
Light (Red)
PS + Light
Cell not transparent
Energy is absorbed
Reactive oxygen species
Oxidative stress
Cell
Cell Dies!!

5. Chemical Targeting

6. Nanomolecular Delivery
Proprietary sensitiser formulation
20 nm nanoparticles containing sensitiser
Cationic surface charge targets cancer
Reduced sensitisation of healthy tissue
Eyes
Skin
Rapid clearance
1wk vs 6

7. Nanomolecular Delivery
Accumulation of sensitizer in skin of Bufo Marinus with nanomolecule
Same sensitizer and same dose without nanomolecule formula

8. Gentle Death High dose: necrosis Minimum dose: apoptosis
Sensitiser bound to mitochondrial membrane
Cleave Bcl-2 / Bcl-XL
Loss of mitochondrial membrane potential
Programmed cell death follows

9. S. S. Stylli and A. H. Kaye, J. Clin. Neurosci. 13, 709-717 (2006)
PDT of Cancer
Barret’s Oesophagus
Adjunct therapy for solid tumours
Systemic administration
Non-surgical debulking
Killing microscopic remnants
Topical application for non-melanoma SC
Glioblastoma Multiforme at RMH
50% survival at 10 yr, vs ~5% at 2 yr chemo
S. S. Stylli and A. H. Kaye, J. Clin. Neurosci. 13, (2006)

10. PDT Causes in-situ Vaccination
Adaptive immunity frequently observed
Remote metastases controlled / eliminated
Tc / NK cells, macrophages
Animal models resistant to rechallenge
Adoptively transferable
Inflammation due to necrosis, immune response due to apoptosis?
F.H. van Duijnhoven et al., Immunobiol. 207, (2003).

11. Activating the Immune System
Because PDT creates a perfect vaccination against the cancer in the patients body, the immune system immediately begins to attack the cancer.
With antibody therapy the suppressor t-cells are activated.
When killing a large tumor up to 95% of the bodies white cells rush to attack the cancer

12. Disabling the Defense
Cancer mounts a defense against the immune system.
T-cells are converted to suppressor cells which suppress new TIL.
Immature myeloid cells are converted to suppressors via ROS.
Antibodies disable the defense systems mounted by cancer to enable immune attack

13. Risk Factors with PDT
High level necrotic kills can cause swelling and inflammation- severe risk for brain tumors.
Even with apoptotic kills the amount of cancer killed can be huge.
Toxin load can be challenging for hepatic and renal elimination, so maintainance of organ health is vital.

14. Absorption/Fluorescence Spectra
λ = 685 nm
(excitation)
Fluorescence
detection
Absorption
Emission

15. Detection of Fluorescence
Laser excitation
Near-IR fluorescence
Camera with IR filter
Laser: 685nm
IR: nm

16. Image on PC Screen

17. Lymphatic Involvement
When cancer is not present in lymph nodes, no fluorescence is seen, as in the left picture above.
When cancer is present, photodynamic fluorescence is very obvious. A few minutes of laser will resolve this condition.

18. Metastatic Bone Cancer
Patient 2: metastasis in the manubrium
Before Treatment After Treatment

19. Metastatic Bone Cancer
Skull mets
Ankle mets

20. Post-Salvage Breast Cancer
Following surgery, chemotherapy and radiotherapy

21. Post-Salvage Breast Cancer
Following Photodynamic Therapy

22. Post-Salvage Breast Cancer

23. Psoriasis Active leukocytes accumulate sensitiser
Topical PDT of skin autoimmune disorders
Psoriasis treated with our sensitiser
Two weeks later

24. Scleroderma treated with our sensitiser
Scleroderma Treated over two years ago
No indication of return to date
Scleroderma treated with our sensitiser

25. Multiple Sclerosis Before treatment After treatment
Multiple Sclerosis treatment is remarkably easy. A one hour infusion with laser illumination at the same time resets the immune system resulting in long lasting remission of symptoms

26. Diabetes Diabetes Mellitus type I has been treated in animal models.
Mice genetically programmed to develop DM I treated with PDT have a 60% lower chance of developing DM I.
Both types of Diabetes are now being considered as autoimmune diseases.
In one diabetic patient treated for cancer, blood sugar levels dropped from 10+ to six range within days after treatment.

27. Diabetic Wound Healing
Wounds which normally don’t heal for days or weeks can be treated with a topical application of sensitizer and a few minutes of laser. Wound healing proceeds normally after treatment

28. Bacteria Golden Staph has been tested to 20 generations of LD 50 kills
It has never shown indication of developing resistance to PDT.
PDT for golden staph can be delivered fast and cost effectively.
In Staph from recent injuries or surgeries, the sensitizer can be administered topically and will absorb through the wound.
Bloodborne golden staph can be treated with IV infusions.

29. Conclusion PDT: a clinical reality in most developed countries
But Australia is trailing ~15 years behind
No sensitiser approved for systemic use
Locally developed and manufactured:
Portable laser, >5W at present and >10W planned
Photosensitisers: systemic, intratumoural, topical
IR camera and uniform illumination

30. Questions?